Little is known regarding the effect of chronic changes in neuronal activity on the extent of collateral sprouting by identified CNS neurons. We have investigated the relationship between activity and sprouting in oxytocin (OT) and vasopressin (VP) neurons of the hypothalamic magnocellular neurosecretory system (MNS). Uninjured MNS neurons undergo a robust collateral-sprouting response that restores the axon population of the neural lobe (NL) after a lesion of the contralateral MNS (). Simultaneously, lesioned rats develop chronic urinary hyperosmolality indicative of heightened neurosecretory activity. We therefore tested the hypothesis that sprouting MNS neurons are hyperactive by measuring changes in cell and nuclear diameters, OT and VP mRNA pools, and axonal cytochrome oxidase activity (COX). Each of these measures was significantly elevated during the period of most rapid axonal growth between 1 and 4 weeks after the lesion, confirming that both OT and VP neurons are hyperactive while undergoing collateral sprouting. In a second study the hypothesis that chronic inhibition of neuronal activity would interfere with the sprouting response was tested. Chronic hyponatremia (CH) was induced 3 d before the hypothalamic lesion and sustained for 4 weeks to suppress neurosecretory activity. CH abolished the lesion-induced increases in OT and VP mRNA pools and virtually eliminated measurable COX activity in MNS terminals. Counts of the total number of axon profiles in the NL revealed that CH also prevented axonal sprouting from occurring. These results are consistent with the hypothesis that increased neuronal activity is required for denervation-induced collateral sprouting to occur in the MNS. (+info)

(2/970) Hormonal regulation of glutamate receptor gene expression in the anteroventral periventricular nucleus of the hypothalamus.

Glutamate plays an important role in mediating the positive feedback effects of ovarian steroids on gonadotropin secretion, and the preoptic region of the hypothalamus is a likely site of action of glutamate. The anteroventral periventricular nucleus (AVPV) of the preoptic region is an essential part of neural pathways mediating hormonal feedback on gonadotropin secretion, and it appears to provide direct inputs to gonadotropin releasing hormone (GnRH)-containing neurons. Immunohistochemistry and in situ hybridization were used in this study to define the distribution and hormonal regulation of glutamate receptor subtypes in the AVPV of juvenile female rats. Neurons that express the NMDAR1 receptor subtype are abundant in the AVPV, as are cells that express AMPA receptor subtypes (GluR1, GluR2, and GluR3 but not GluR4), and the AVPV appears to contain a dense plexus of NMDAR1-immunoreactive presynaptic terminals. However, AVPV neurons do not seem to express detectable levels of kainate receptor (GluR5, GluR6, and GluR7) or metabotropic receptor (mGluR1-6) subtypes. Treatment of ovariectomized juvenile rats with estradiol induced expression of GluR1 mRNA but did not alter levels of GluR2 or GluR3 mRNA. Treatment of estrogen-primed ovariectomized juvenile rats with progesterone caused an initial increase in GluR1 mRNA expression, followed by a small decrease 24 hr after treatment. In contrast, estrogen appears to suppress levels of NMDAR1 mRNA in the AVPV, which remained unchanged after progesterone treatment. Thus, one mechanism whereby ovarian steroids may provide positive feedback to GnRH neurons is by altering the sensitivity of AVPV neurons to glutamatergic activation. (+info)

Fos immunoreactivity was used to map the neuronal population groups activated after sodium ingestion induced by peritoneal dialysis (PD) in rats. Oxytocin immunoreactivity in combination with Fos immunoreactivity was also analyzed to evaluate whether the oxytocinergic neurons of the paraventricular nucleus of the hypothalamus (PVN) are activated during the satiety process of sodium appetite. Sodium ingestion stimulated by PD produced Fos immunoreactivity within defined cells groups of the lamina terminalis and hindbrain areas such us the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. On the other hand, particular parvocellular and magnocellular oxytocinergic subdivisions of the PVN and supraoptic nucleus were double labeled after PD-induced sodium consumption. Approximately 27 and 2.1%, respectively, of the activated dorsomedial cap and parvocellular posterior subnuclei of the PVN, which project to the hindbrain, were oxytocinergic. Our data indicate that specific neuronal groups are activated during the satiety process of sodium appetite, suggesting they may form a circuit subserving sodium balance regulation. They also support a functional role for the oxytocinergic neurons in this circuit. (+info)

SR146131 is a potent and selective agonist at cholecystokinin subtype 1 (CCK1) receptors in vitro. The present study evaluates the activity of the compound in vivo. SR146131 completely inhibited gastric and gallbladder emptying in mice (ED50 of 66 and 2.7 micrograms/kg p.o., respectively). SR146131 dose dependently reduced food intake in fasted rats (from 0.1 mg/kg p.o.), in nonfasted rats in which food intake had been highly stimulated by the administration of neuropeptide Y (1-36) (from 0.3 mg/kg p.o.), in fasted gerbils (from 0.1 mg/kg p.o.), and in marmosets maintained on a restricted diet (from 3 mg/kg p.o.). SR146131 (10 mg/kg p.o.) also increased the number of Fos-positive cells in the hypothalamic paraventricular nucleus of rats. Locomotor activity of mice was reduced by orally administered SR146131 (from 0.3 mg/kg p.o.). When administered intrastriatally, SR146131 elicited contralateral turning behavior in mice. Furthermore, orally administered SR146131 (0.3-10 mg/kg), also reduced the levels of cerebellar cyclic GMP. Finally, SR146131 (0.1 microgram/kg to 1 mg/kg, p.o.) significantly and dose dependently antagonized fluphenazine-induced mouth movements in rats. The CCK1 antagonist SR27897B prevented all the effects of SR146131. Conversely, SR146131 was unable to elicit any agonist or antagonist effects in a model of CCK2 receptor stimulation in vivo. SR146131 is a very potent and selective nonpeptide CCK1 agonist in vivo. SR146131 is more potent than any other CCK1 agonists reported to date. Because pharmacodynamic studies suggest that SR146131 should have a high absolute bioavailability, it may be a promising drug for the treatment of eating and motor disorders in humans. (+info)

As a first step in determining possible influences of the newly discovered estrogen receptor (ER)-beta on reproduction, we have localized mRNA for ER-beta within the male sheep hypothalamus using in situ hybridization and a rat ER-beta cRNA probe. Highest amounts of hybridization signal were observed in the preoptic area (POA), bed nucleus of the stria terminalis, paraventricular nucleus, and supraoptic nucleus. Relatively moderate amounts of hybridization signal were observed in the retrochiasmatic area (RCH), anterior hypothalamic area, dorsomedial hypothalamus, and lateral hypothalamus. Only a low level of hybridization signal was observed in the ventromedial hypothalamus, suprachiasmatic nucleus, and arcuate nucleus. The presence of ER-beta mRNA in several areas of the male sheep hypothalamus suggests multiple functions for this receptor. The distribution of ER-beta in the ovine hypothalamus was similar to that described for the rat, suggesting a high degree of functional conservation across species. A role for ER-beta in influencing reproduction is suggested by its presence in the POA and RCH, regions of the hypothalamus that control reproduction. (+info)

1. We have recently shown that neurones in the rostral region of the medial vestibular nucleus (MVN) develop a sustained increase in their intrinsic excitability within 4 h of a lesion of the vestibular receptors of the ipsilateral inner ear. This increased excitability may be important in the rapid recovery of resting activity in these neurones during 'vestibular compensation', the behavioural recovery that follows unilateral vestibular deafferentation. In this study we investigated the role of the acute stress that normally accompanies the symptoms of unilateral labyrinthectomy (UL), and in particular the role of glucocorticoid receptors (GRs), in the development of the increase in excitability in the rostral MVN cells after UL in the rat. 2. The compensatory increase in intrinsic excitability (CIE) of MVN neurones failed to occur in animals that were labyrinthectomized under urethane anaesthesia and kept at a stable level of anaesthesia for either 4 or 6 h after UL, so that they did not experience the stress normally associated with the vestibular deafferentation syndrome. In these animals, 'mimicking' the stress response by administration of the synthetic GR agonist dexamethasone at the time of UL, restored and somewhat potentiated CIE in the MVN cells. Administration of dexamethasone in itself had no effect on the intrinsic excitability of MVN cells in sham-operated animals. 3. In animals that awoke after labyrinthectomy, and which therefore experienced the full range of oculomotor and postural symptoms of UL, there was a high level of Fos-like immunoreactivity in the paraventricular nucleus of the hypothalamus over 1.5-3 h post-UL, indicating a strong activation of the stress axis. 4. The GR antagonist RU38486 administered at the time of UL abolished CIE in the rostral MVN cells, and significantly delayed behavioural recovery as indicated by the persistence of circular walking. The mineralocorticoid receptor (MR) antagonist spironolactone administered at the time of UL had no effect. 5. Vestibular compensation thus involves a novel form of 'metaplasticity' in the adult brain, in which the increase in intrinsic excitability of rostral MVN cells and the initial behavioural recovery are dependent both on the vestibular deafferentation and on the activation of glucocorticoid receptors, during the acute behavioural stress response that follows UL. These findings help elucidate the beneficial effects of neuroactive steroids on vestibular plasticity in various species including man, while the lack of such an effect in the guinea-pig may be due to the significant differences in the physiology of the stress axis in that species. (+info)